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The Journal of Neuroscience, June 1, 1999, 19(11):4305-4313
Sensory Impairments and Delayed Regeneration of Sensory Axons in
Interleukin-6-Deficient Mice
Jian
Zhong1,
Irmgard D.
Dietzel1,
Petra
Wahle2,
Manfred
Kopf3, and
Rolf
Heumann1
1 Lehrstuhl für Molekulare Neurobiochemie and
2 Lehrstuhl für Allgemeine Zoologie und
Neurobiologie, Ruhr-Universität Bochum, 44780 Bochum Germany, and
3 Max-Planck-Institut für Immunobiologie,
Stübeweg 51, 79108 Freiburg, Germany
Interleukin-6 (IL-6) is a multifunctional cytokine mediating
inflammatory or immune reactions. Here we investigated the possible role of IL-6 in the intact or lesioned peripheral nervous system using
adult IL-6 gene knockout (IL-6 /) mice. Various
sensory functions were tested by applying electrophysiological, morphological, biochemical, and behavioral methods. There was a 60%
reduction of the compound action potential of the sensory branch of
IL-6/ mice as compared with the motor branch in
the intact sciatic nerve. Cross sections of L5 DRG of
IL-6/ mice showed a shift in the relative size
distribution of the neurons. The temperature sensitivity of
IL-6/ mice was also significantly reduced.
After crush lesion of the sciatic nerve, its functional recovery was
delayed in IL-6/ mice as analyzed from a
behavioral footprint assay. Measurements of compound action potentials
20 d after crush lesion showed that there was a very low level of
recovery of the sensory but not of the motor branch of
IL-6/ mice. Similar results of sensory
impairments were obtained with mice showing slow Wallerian degeneration
(Wlds) and a delayed lesion-induced recruitment of
macrophages. However, in contrast to WldS mice, in
IL-6/ mice we observed the characteristic
lesion-induced invasion of macrophages and the upregulation of
low-affinity neurotrophin receptor p75 (p75LNTR) mRNA levels identical
to those of IL-6+/+ mice. Thus, the mechanisms
leading to the common sensory deficiencies were different between
IL-6/ and WldS mice.
Altogether, the results suggest that interleukin-6 is essential to
modulate sensory functions in vivo.
Key words:
interleukin-6; compound action potential; sensory
fiber; motor fiber; temperature sensitivity; L5 DRG; neuron; sciatic
functional index; regeneration; WldS; p75LNTR-mRNA; macrophages
Copyright © 1999 Society for Neuroscience 0270-6474/99/19114305-09$05.00/0
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